A host-cell-selected variant of influenza B virus with a single nucleotide substitution in HA affecting a potential glycosylation site was attentuated in virulence for volunteers

Summary An influenza B virus was passaged in man (virus A) and then in human embryo trachea (C) and into embryonated eggs (D) or directly into eggs (B). Virus A, B, and C had the same (cell-like) haemagglutinin phenotype on reaction with selected monoclonal antibodies while D had an egg-like phenotype. The viruses were administered at a dose of 1,000 TCD₅₀ (for MDCK cells) by intranasal inoculation to groups of 27 or 28 volunteers. Viruses A, B, and C all produced disease in six to eight volunteers, whereas D produced no illness and only four volunteers were infected. The viruses shed by the volunteers were indistinguishable from those with which they were inoculated. The haemagglutinin genes of the viruses were sequenced and changes were detected indicating amino acid substitutions at position 196–198 in the attenuated egg-grown virus D whereby a potential glycosylation site present in the other viruses was lost.     

Biochemical interactions between methotrexate and 1-β-d-arabinofuranosylcytosine in hematopoietic cells of children: a Pediatric Oncology Group study

Summary Children with acute lymphocytic leukemia (ALL) in remission were treated with overlapping sequential infusions of methotrexate (MTX) and 1--d-arabinofuranosylcytosine (araC) as part of continuation therapy. The doses and the sequence were chosen to mimic conditions that produced greater than additive antineoplastic activity with these two drugs in preclinical studies. To assess the potential for the drug combination to exhibit greater than additive effect in vivo, we investigated several biochemical parameters that had been associated with synergism in vitro. Because the patients were in remission, the intracellular parameters could only be measured in cytologically normal hematopoietic cells. We observed that (1) the mean plasma concentrations of MTX and araC were above those required to obtain a greater than additive cytotoxicity with the two drugs in tissue culture; (2) MTX did not have a significant antipurine effect in bone marrow mononuclear cells; (3) the mean intracellular concentration of deoxycytidine triphosphate (dCTP) was significantly lower after treatment with the drug combination than after therapy with araC alone; and (4) the ratio of araC triphosphate (araCTP) to dCTP was 2.6 times higher after treatment with the combination than after araC alone. These results indicate that it is possible to achieve in patients the biochemical conditions associated with the greater than additive antineoplastic activity of MTX and araC in vitro.Abbreviations ALL acute lymphocytic leukemia - araC 1--d-arabinofuranosyluracil - araCTP araC triphosphate - araU 1--d-arabinofuranosyluracil - dNTPs deoxyribonucleoside triphosphates - MTX methotrexate - TCA trichloroacetic acid Supported in part by grants from the National Cancer Institute, National Institutes of Health (CA-38 053; CA-33572, CA-32278, CA-38 859, CA-29 691, and CA-30 969). Preliminary reports on the biochemical data were published by E. M. N., A. M. T., and D. P. inProc Am Assoc Cancer Res 24: 133 (1983) and those on the clinical data, by R. A K., E. M. N., D. P. R. B. R., M. B. H., Y. R., and A. I. F. inProc Am Soc Clin Oncol 3: 201 (1984)     

Professional associations and managed care. How four provider groups are helping their members

Managed care is facilitating rapid change in the day-to-day practice of many addiction treatment and mental health professionals. It is only natural, therefore, that the associations representing the various disciplines in behavioral healthcare should seek to present short- and long-term plans, advice, and programs for their members. We have asked leaders from four prominent groups to present what their organizations are doing today to assist professionals in adapting to the new realities of the healthcare system. The comments below are by no means conclusive, and are representative of a few efforts and thoughts. It is our mission at Behavioral Healthcare Tomorrow to provide an independent platform for dialogue in the world of mental health and addiction treatment. It is our hope that the proposals and ideas published here stimulate even more planning amongst providers as managed care assertively enters public sector services.     

Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient

Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron discase (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/ protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.     

Bloodborne exposures at a United States Army Medical Center

With the ultimate goal of minimizing exposures, we conducted a hazard analysis on bloodborne disease transmission at our hospital to identify appropriate control interventions. We utilized basic principles of occupational epidemiology to gather information on the severity and extent of exposures. Because we suspected inadequate reporting of needlestick injuries, we collected 339 reported exposures of health care workers; we conducted a survey of all workers requiring universal precautions training for bloodborne pathogens. The annual incidence of exposures reported was 93.7 per 1000 workers who required this training. Sharps accounted for 83.5 percent of these exposures. Exposure sources demonstrated 4.3 percent positive for HIV, 4.4 percent positive for hepatitis B, and 7.1 percent positive for hepatitis C. The survey indicated that blood/body fluid exposures were underreported by at least fourfold. House officers were most at risk. At-risk behaviors were identified by the significant differences in knowledge of HIV transmission and work practices between groups reporting no or single exposures versus groups reporting multiple exposures. Increased emphasis should be placed on education, reporting exposures, and training house officers in procedures requiring the use of hollow bore needles. This study shows how the use of occupational epidemiology principles and methods were utilized in conducting a thorough hazard analysis and in identifying appropriate control methods.     

What do patients want and do we want to know? A review of patients' requests of psychiatric services

OBJECTIVE: A systematic review was conducted of the literature concerning patients' requests of psychiatric care in order to identify the types of requests patients make, psychiatrists' perceptions of their patients' requests, and the relationship between requests and the outcome of care. METHOD: A total of 28 published original articles which fulfilled specific inclusion criteria were reviewed. RESULTS: The studies showed that there are certain core requests that patients make irrespective of the type of service attended. Patients mainly request psychological approaches, and the most common requests are for 'clarification', 'psychological expertise' and 'psychodynamic insight'. There is evidence that patients normally feel inhibited about making requests, and that psychiatrists often fail to identify what their patients want. CONCLUSION: The majority of patients attending psychiatric services have requests which they will express when encouraged to do so, but little is known about the relationship between patients' requests and the outcome of care. Recommendations are made for future research.     

Neural pathway from the olfactory bulbs regulating tonic gonadotropin secretion

Removal of the olfactory bulbs of male golden hamsters results in a marked increase in tonic gonadotropin, prolactin and testosterone secretion which counteracts inhibitory effects of manipulations such as maintenance on short photoperiod, food restriction or treatment with gonadal steroids. The bulbectomy-induced increase in hormone secretion is interpreted to reflect a tonic inhibitory influence of the olfactory bulbs. This inhibition is not dependent upon chemosensory stimulation and may be mediated by olfactory bulb fibers projecting through the lateral olfactory tract to or through the olfactory tubercle. This review will relate these studies conducted on hamsters to results in other species, such as the rat, where the olfactory bulbs enhance serum gonadotropin levels.